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Author: Subject: LSD on antipsychotics
karlos³
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[*] posted on 24-4-2020 at 20:03


What, why would you need and want any control, its a psychedelic experience, you're not driving a car :o
That sounds like a recipe for a long lasting disturbance between you and psychedelics, with such an underlying issue, especially since the fear of loosing control is something very deeply seated...
Wouldn't be surprised if the right person could fix that, which in turn would enable you to use those compounds again.
But I am just guessing based on those two statements, maybe you can't use them anymore because of something completely different, something neurological/or some medication resulting in neurological changes that make them ineffective for you?
I pity you, but I am sure(or hope) that it isn't as horrible as the OP and the prospect that whatever it is will be over soon, is already in reach for you.
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outer_limits
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[*] posted on 24-4-2020 at 20:55


You're right - maybe a will to keep any control was too strong ;)
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mackolol
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[*] posted on 25-4-2020 at 05:41


Quote: Originally posted by karlos³  
What, why would you need and want any control, its a psychedelic experience, you're not driving a car :o


It all depends on you, how familiar are you with these compounds and how well can you control yourself and of course how big dose you take.
For example my friend on new years eve, took 150ug of LSD, pretty normal dose, but no one from his company couldn't tell that he was tripping although they knew that and he definitely was. Of course he couldn't drive a car
So you can control yourself on psychedelics

Quote: Originally posted by outer_limits  
Sure, in comparison to stimulant drugs they are almost harmless. But to be honest - you can never be sure that they won't do different type of damage.
I'm not sure if there is something which you can name "taking in responsible manner" without the psychologist who knows what psychedelics are and how to handle both: them and their possible adverse effects.
If you asked me few years ago I would answer totally the same. Now I am not so sure and I think that taking psychedelic drugs is similar to a bungee jumping. You don't know the crew; you don't know the gear - you don't have any control. Even if you think you have, you don't.


And neither do I think that they can cause psychical damage. Psychedelics can deepen your psychological problems or cause them if you're prone to them. But if you're totally healthy, they don't cause damage.

[Edited on 25-4-2020 by mackolol]
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outer_limits
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[*] posted on 25-4-2020 at 09:42


Quote: Originally posted by mackolol  

Psychedelics can deepen your psychological problems or cause them if you're prone to them. But if you're totally healthy, they don't cause damage.


So... you just wrote that they don't do damage but they do if you have those 'famous predispositions'.
There are such predispositions but usual psychedelic drug user has no knowledge about mental health, psychiatry and psychology. It's very common to hear the words you wrote but it's a bullshit.

Imagine such a situation. You are healthy person without any mental/psychological issues that you know about.
After a psychedelic experience your state changed to for example: paranoid or suicidal, requiring long medical treatment.
So, before psychedelic experience you lived normally, after the trip you have a really hard time and possibilities to recover are not known. Your state has dramatically worsened - isn't a damage?

I am not against psychedelic drugs, but there is no need to defend them in such a way. Their neurological mechanism of action is so profound that even healthy people can develop PTSD after a really bad experience. As any other biologically active compound - they have adverse effects. And honestly, if somebody says they don't have any - he's a liar. Even if they are preety rare they still exists.

You can always say that 'somebody was prone to such problems' - but without any scientific background and professional approach it's just a lie.
You could say that only after psychological and psychiatric screenings conducted by experienced professionals.

[Edited on 25-4-2020 by outer_limits]
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[*] posted on 25-4-2020 at 12:57


Yes of course, some of the LSD users can develop PTSD after very profound and bad experience. But there are also very heavy users of psychedelics, that take Acid once or twice a week. They become quite weird, especially sociable, but they and don't seem to have mental issues.
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[*] posted on 15-12-2021 at 00:55


Quote: Originally posted by mackolol  
Psychedelics don't work when on antipsychotics no matter how high dose will you take. You could take as well 5mg of LSD.
If you are having a bad trip, or you just want to end your psychedelic high solution is just to take antipsychotics or benzodiazepines.


[Edited on 5-4-2020 by mackolol]


I know I'm way late for the parade, but I just joined the board and as it happens I cam address the question of psychedelic interactions with antipsychotics about as definitively as you are going to get. I'm an MD/PhD. and my research was on central serotonergic function. This is solidly within my professional sphere.

The effect pf antipsychotics on psychedelics all boils down to 5HT2A receptor function. Classic psychedelics, both indoleakylamines and phenylethylamines, produce their effects through agonist activity at the 2A receptor. Not all 2A agonists have psychedelic effects, ergotamine for example. The reason is ligand directed signaling. Activation of the 2A receptor can activate multiple second messenger pathways, psychedelic agonists have a particular profile of intracellular effects on activation. Read all about it here. Lots of good references in that paper too.

For example, work done mostly in Franz Vollenweider's lab, found that in healthy volunteers given LSD or psilocybin, the 5HT2A antagonist ketanserin blocks their psychedelic effects. This is where antipsychotics come into it. Newer, 'atypical' antipsychotics are distinguished from classic 'typical' antipsychotics that block dopamine D2 receptors, by also having effects on the serotonin system mostly via antagonist activity at 5HT2A receptors. In some atypicals such as risperidone, 2A antagonism is extremely strong even at very low doses. In the case of risperidone, at or below the lowest effective antipsychotic dose.

But not all antipsychotics will block psychedelics. Older 'typical' antipsychotics do not. Haloperidol, a high potency selective D2 antagonist has little effect on the trip itself. Benzodiazepines will sedate you and make you less anxious abiut the intense psychedelic effects, but has little effect on the trip itself.

True story. I was working one night at in the psych ER at the county hospital of a major US city to remain nameless. Heard about a college student coming in freaking out after taking a large number of mushrooms he'd cultivated. Normally I didn't find out about cases like that until they have mostly cleared and show up on the psych side of the ER. He was freaking out less when he got there (his 'better living through chemistry; T-shirt was a nice touch), but he was almost completely incoherent, unable to string together 2 or 3 words that went well together. IIRC, he had wet himself. Tried to tell him I was giving him a medication to stop the trip and gave him 0.5 or 1mg (can't remember it was 15+ years ago), risperidone by mouth. Usual dose is 1 to 6 mg a day. Came back about 40-45 min later. He is sitting up, in scrubs to replace the wet pants, speaking in complete sentences, damn near stone cold sober. Talking with him, he'd gotten a bumper crop his first time growing mushrooms and severely underestimated the potency of fresh picked and dried mushrooms over ones he had bought. So about 60 minutes after arriving unable to speak, he was getting ready to be discharged and go home. And not take so many at once next time.

Paloperidone is, like risperidone a high potency antagonist at D2 and the 5HT2A (Ki = 0.4nM). It is entirely to be expected that it will prevent psychedelic drug effects. Other atypical antipsychotics have different affinities for 5HT2A receptors and their ability to block psychedelics will be proportional to their 5HT2A blockade in vivo. The ones that have the highest affinity will do the best in terminating a trip. Of import, some of these notably risperidone may be available as quick acting orally disintegrating tablets.

The alcohol effect the OP described is idiosyncratic as it is not an general effect of atyptical antipsychotics nor of paloperidone in particular. If anything, they are likely to increase sedation from alcohol in proportion to their own sedative effects.

The obligatory disclaimer. I am not giving medical advice, nor forming any type of doctor-patient relationship with anyone. Nor am I encouraging use of psychedelics in any setting.

My terrible typing skills, arthritic thumbs, and ability to read what I intended to write not what I wrote ask you to tolerate ny uncorrected typos.

[Edited on 15-12-2021 by DrRadium]

[Edited on 15-12-2021 by DrRadium]

[Edited on 15-12-2021 by DrRadium]
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[*] posted on 15-12-2021 at 02:02


Quote: Originally posted by outer_limits  

It could be dangerous. I don't know if results of this study are relevant to LSD also but repeated administration of psilocybin can damage blood vessels and lead to ischaemic disease.
Polish medical academy conducted a research:


Quote:

MORPHOLOGICAL CHANGES IN MYOCARDIUM AND CORONARY VESSELS OBSERVED AFTER PSILOCIN ADMINISTRATION IN EXPERIMENTAL CONDITIONS Abstract Introduction and aims: Apart from psychodysleptic effects, natural hallucinogens may exhibit organ toxicity e.g., to the cardiovascular system. The aim of this paper is to evaluate morphological changes, such as histopathological and morphometric ones, observed in experimental conditions in rats under repeated administration of psilocin - an alkaloid present in hallucinogenic mushrooms, also known as magic mushrooms. Materials and methods: The study was performed on three-month-old male Wistar rats repeatedly given psilocin. The post-mortem biological material was collected in order to analyze morphological changes in the myocardium and coronary vessels using histopathological and morphometric studies. Results: Morphological changes occurred in the myocardium and coronary vessels in the form of subendocardial fibrosis, increase in the volume of loose connective tissue of the stroma, perivascular fibrosis and thickening of the vascular walls. Conclusion: Repeated administration of psilocin in rats is associated with morphological changes both in the myocardium and the coronary vessels walls. Keywords: Psylocin, hallucinogenic mushrooms (magic mushrooms), cardiotoxic effect. (Received: 24.05.2017; Revised: 25.05.2017; Accepted: 31.05.2017)



Cardiac effects from serotonergic drugs are linked to effects from activation of another serotonin receptor, the 5HT2B, in thr heart. Chronic agonism at the 2B can cause cardiac fibrosis and valvulopathy, apparently via simulation of cardiac fibroblast activity. This is what got fenfluramine pulled from the market. This id now something new serotonergic drugs are screened for. Of note, it really does require chronic dosing, single doses don't carry lsubstatial risk, but potent 2B agonists taken frequently have serious cardiac risks. And here is a full text review compliments of the NIH.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179857/

Psilocybin/psilosin are partial agonists at 5HT2B receptors, with moderate affinity, but low efficacy in activating the receptor (the partial agonism is weak). MDMA and metabolites have substantial 5HT2B agonist activity. The NIMH Psychoactive Drug Screening Program run by Bryan Roth provide data about receptor binding profiles for both old and new drugs, and proved useful in IDing hazardous drugs when the link between cardiac fibrosis and 5HT2B agonism was detected. PDSP data is available to the public here.
One caveat to keep in mind is that the conditions in which the binding is tested is too often far from physiologic, so real in vivo binding many differ.

Microdosing creates issues obviously. On one hand, it's chronic dosing which is where the danger lies. OTOH it's micro, so it is possible that dosing is under threshold for biological effects. It's unclear at present but is on minds of scientists in the field.

Digging up references I came across an online literature review by an exercise physiologist on of the safety of psilocybin in regards to cardiac fibrosis that was an easy read and does a good job of laying out the issues involved https://drbillsukala.com/psilocybin-heart-valve-damage/

One last reference, a huge one on psychedelics by Dave Nichols, who curiously, looks (and whose voice sounds) a lot like a classic American version of Santa Claus.


[Edited on 15-12-2021 by DrRadium]
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karlos³
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[*] posted on 15-12-2021 at 02:43


Quote: Originally posted by DrRadium  
Quote: Originally posted by mackolol  

True story. I was working one night at in the psych ER at the county hospital of a major US city to remain nameless. Heard about a college student coming in freaking out after taking a large number of mushrooms he'd cultivated. Normally I didn't find out about cases like that until they have mostly cleared and show up on the psych side of the ER. He was freaking out less when he got there (his 'better living through chemistry; T-shirt was a nice touch), but he was almost completely incoherent, unable to string together 2 or 3 words that went well together. IIRC, he had wet himself. Tried to tell him I was giving him a medication to stop the trip and gave him 0.5 or 1mg (can't remember it was 15+ years ago), risperidone by mouth. Usual dose is 1 to 6 mg a day. Came back about 40-45 min later. He is sitting up, in scrubs to replace the wet pants, speaking in complete sentences, damn near stone cold sober. Talking with him, he'd gotten a bumper crop his first time growing mushrooms and severely underestimated the potency of fresh picked and dried mushrooms over ones he had bought. So about 60 minutes after arriving unable to speak, he was getting ready to be discharged and go home. And not take so many at once next time.

Thank you for joining, what an interesting biography! :)

I have myself experienced exactly the same.
Although, the "psychedelic" was actually a deliriant(it was datura flower whiskey), and the antidote was haloperidol....
I remember sitting on a sofa, after having drunk that stuff from the little plastic beaker they gave me...

And how I, shyly, approached them at their counter an half hour later, asking wtf happened and why I'm there....
That was after the haldol "kicked in" and I saw reality again as what it is.
Lesson learned was, not to use nightshade derived deliriants ever again....




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[*] posted on 15-12-2021 at 16:15


Datura flowers are mean stuff.

Especially if you take them together with mescaline.:(

CmnRB4-XEAAuA_R.jpg - 398kB

Going rock climbing with Bob Dobbs.

[Edited on 16-12-2021 by SWIM]




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[*] posted on 19-12-2021 at 13:58


Quote: Originally posted by SWIM  
Datura flowers are mean stuff.

Especially if you take them together with mescaline.:(
[Edited on 16-12-2021 by SWIM]


I don't know why anyone would want to take perfectly good mescaline and f-it up with scopalamine. Other than maybe a transderm scop patch for nausea.
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[*] posted on 19-12-2021 at 15:13


Quote: Originally posted by DrRadium  
Quote: Originally posted by SWIM  
Datura flowers are mean stuff.

Especially if you take them together with mescaline.:(
[Edited on 16-12-2021 by SWIM]


I don't know why anyone would want to take perfectly good mescaline and f-it up with scopalamine. Other than maybe a transderm scop patch for nausea.


This combination was used somewhere in South America at one time.
However just because it was a practice of some indigenous peoples doesn't mean it was a good idea.
I think William Emboden maybe mentioned this combination in one of his works.




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[*] posted on 20-12-2021 at 09:58


Just to add some info about alcohol.

Alcohol overlaps the 5HT2A and 5HT2B receptor pathways

800px-Release,_Reuptake,_and_Metabolism_Cycle_of_GABA.png - 208kB

In this photo you see gamma aminobutryic acid cycling. GABA is mediated by alcohol directly.

The ion channel GIRK is mediated by the 5HT2A and 5HT2B circuits which are mediated by LSD and others. Things like apiperazole can block or modulate GIRK and other ion channels indirectly.

What does this mean in plain english, well, basically you have a very high tolerance for alcohol, not because you metabolize it faster but rather because your body requires larger doses to feel the effects. Be careful as this also means you still have the same toxicity to it, thus you may drink more anticipating a reaction and you will be much closer to the LD50. Id steer clear of this as the GABA modulation will mess up your apiperazole cycle.

A good example of the issues that arise here are the deadly combo of benzodiazepines and alcohol. The GABA receptors have binding affinities for benzos and other related ones.

Paliperidone is a 5HT2,3,4 antagonist (as far as we can tell) and thus directly interacts with other pathways. A photo below shows one of the many interactions, specifically GIRK in this case. But there are probably between 10 and 40 interactions depending on what part of the body it was absorbed. The 5HT family is all over the body in varying amounts. The main location is the brain, where it has the highest concentration of proteins in this family with exception to 5HT3.


5-Hydroxytryptamine-Receptor-Family-1.png.jpg - 43kB


To give you insight on why drugs like Risperidone are antidotes:
Risperidone is a potent antagonists, and this means theh will selectively compete with other chemicals to bind to the protein. So paliperidone is actually even stronger than risperidone (which is given less nowadays) and can actually outcompete the normals agonists. The point of the medication when not used for antidote purposes is that it stops overactive receptors (because schizophrenia does that).

[Edited on 12-20-2021 by aab18011]

[Edited on 12-20-2021 by aab18011]




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